This will be a phase II randomized partially placebo-controlled, 4-arm trial comparing amprenavir (APV) in a single-PI regimen versus APV in combination with saquinavir (SQVsgc), indinavir (IDV) or nelfinavir (NFV) in HIV-infected subjects currently failing IDV, RTV, SQV or NFV, as reflected by a plasma HIV-1 RNA concentration of >1000 copies/ml. Eligible subjects must be currently failing IDV, NFV, SQV, or RTV as part of a single or dual PI regimen (as evidenced by two consecutive plasma HIV RNA levels > 1000 copies/ml) after at least 16 cumulative weeks of protease inhibitor exposure. Subjects may have prior exposure to up to three protease inhibitors (IDV, RTV, SQV or NFV) including the currently failing regimen. For the purposes of this study, "exposure" to a protease inhibitor is considered >7 cumulative days of treatment. No prior exposure to efavirenz (EFV), amprenavir (APV), abacavir (ABC) or adefovir dipivoxil (ADV) is allowed. Subjects with nevirapine or delavirdine exposure will be premitted to enroll but will be limited to 1.3 of the study population. Prior exposure to NRTIs is allowed. 460 subjects to be enrolled over a 6 month period. Subjects will be stratified for prior PI and NNRTI exposure. All subjects will receive amprenavir (APV), abacavir (ABC), efavirenz (EFV) and adefovir dipivoxil (ADV). Subjects will be selectively randomized to one of four treatment arms as described below. All subjects will have an equal or greater chance of being randomized to a dual-PI arm than the single-PI arm.